AbstractNon-enterica subspecies of Salmonella enterica are rarely associated with human infections. Paradoxically, food safety legislations consider the entire genus Salmonella as pathogenic to humans. Globally, large amounts of seafoods are rejected and wasted due to findings of Salmonella. To inform better food safety decisions, we investigated the pathogenicity of Salmonella Salamae 42:r- and Salmonella Waycross isolated from Nile perch from Lake Victoria. Genome-wide analysis revealed absence of significant virulence determinants including on key Salmonella pathogenicity islands in both serovars. In epithelial cells, S. Salamae showed a weak invasion ability that was lower than the invH mutant of S. Typhimiurium used as negative control. Similarly, S. Salamae could not replicate inside macrophages. Moreover, intracellular replication in S. Waycross strains was significantly lower compared to the wild type S. Typhimurium. Our findings suggest a low pathogenicity of S. Salamae reinforcing the existing literature that non-enterica subspecies are avirulent. We propose that food legislations and actions taken on findings of Salmonella are revisited to avoid wasting valuable sea- and other foods.